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Successful outcome of oral testosterone clinical study | Investor or Media Relations
Diurnal is a European, UK-headquartered specialty pharmaceutical company dedicated to developing lifelong treatments for rare and chronic endocrine conditions.
www.diurnal.com
DITEST™
In addition to its hydrocortisone products, Diurnal’s is also developing a novel formulation of testosterone for the treatment of hypogonadism. Male hypogonadism is defined as testosterone levels below 300ng/dL and, like other endocrine disorders, can be of primary (a dysfunction in the testes) or secondary (a dysfunction in other hormone systems) origin. The crude prevalence of androgen deficiencies in the US male population is estimated to be 6%, making hypogonadism one of the most common endocrine disorders.5 However, the number of men diagnosed with hypogonadism is markedly less at only 500,000 in the United States.
The United States is by far the biggest market for testosterone replacement in the world, estimated at $1.1bn in 2018 ($1.6bn worldwide).6 There are a number of both branded and generic testosterone products approved in the United States. These products are differentiated primarily based on how they are administered. The historic market leader for branded products has been Androgel, a testosterone supplement provided as a topical gel that is applied under the arms. It had peak sales of over $1bn in 2012 but lost significant market share after reports that it (and testosterone therapy more generally) could increase the risk of a heart attack. Additionally, generics of Androgel were launched in 2019.
One of the well-documented risks associated with Androgel has been the exposure of unintended people to the drug, such as the family members of the man taking the supplement. The topical nature of the drug makes physical transference easy, and there have been reports of the wives and prepubescent children of patients developing male secondary sexual characteristics (such as growing a beard) from cross-exposure. These gel-based products carry a black box warning for such issues of transference.
Oral testosterone supplements can avoid these issues of transference, although they make up a smaller portion of the market. Currently available oral products use an undecanoate ester of testosterone, which dramatically improves bioavailability over uncodified testosterone by avoiding first-pass metabolism. However, testosterone undecanoate has a substantial food effect: for instance, Jatenzo must be taken with a high-fat meal (30g of fat or more) to ensure complete absorption and this must be done twice a day. For reference, a tablespoon of butter has 12g of fat. Moreover, Jatenzo has a black box warning for cardiovascular side effects.
Diurnal’s DITEST™ product is a formulation of unmodified testosterone that seeks to avoid the issues of poor bioavailability by using a proprietary, oil-based excipient mixture. It has not been reported on how this excipient mixture avoids the issue of first-pass metabolism, but Diurnal has reported results from a Phase I study (n=25, 24 completed treatment) that showed similar pharmacological parameters to testosterone undecanoate, but without the food effect.
Historically, it has been difficult for new testosterone products to achieve approval due to a combination of factors. This is driven in part by concerns over safety because it was discovered years after the first testosterone products were approved that testosterone replacement could be associated with cardiovascular risks. The agency is requiring companies to rigorously prove that their products are safe, and the increased statistical bar has made it difficult for some products. For instance, the oral testosterone Tlando from Lipocine has been rejected by the FDA three times (and is currently on its fourth submission) due to concerns over the safety of super-physiological concentrations of testosterone. In addition, there has been substantial disagreement between the agency and physician groups regarding clinical definitions of hypogonadism.
Diurnal met the FDA in July 2020 and confirmed with the agency that the product could be evaluated under the 505(b)2 pathway. This pathway is for products where the active pharmaceutical ingredient (in this case testosterone) has already been approved and allows the sponsor to use data from these previous applications in their clinical data package. The FDA guided Diurnal that it could seek approval for its DITEST™ after two additional clinical studies: a multiple ascending dose study and a single Phase III study. Diurnal anticipates filing an IND for the product in Q221 and we expect the dosing study to initiate shortly thereafter.
